Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1762617 (weakness)
 37,932 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tizanidine (Sirdalud) was compared to baclofen (Lioresal) in a randomized, double-blind, cross-over trial. Each medication was introduced over a three week titration period and then maintained at the highest tolerated dose for five weeks. The two treatment phases were separated by a one week drug withdrawal and a two week washout period. Sixty-six patients entered the trial and forty-eight completed both treatment phases. At the end of the trial, neurologists and physiotherapists thought that baclofen was superior on the basis of perceived efficacy and tolerance (p less than or equal to 0.05). Although the efficacy of tizanidine or baclofen was judged as good to excellent by 24 and 39% of patients respectively, this difference was not statistically significant. Muscle weakness was the most common adverse effect. This was significantly more troublesome in patients treated with baclofen. Somnolence and xerostomia were more common in patients treated with tizanidine. Both baclofen and tizanidine appear to be useful adjuncts in the treatment of spasticity in patients with multiple sclerosis. Preference of either drug is tempered principally by side-effects.
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PMID:Tizanidine versus baclofen in the treatment of spasticity in patients with multiple sclerosis. 334 56

The anti-spastic effect of a new drug, tizanidine, was compared with that of baclofen in a double-blind clinical trial; 40 seriously handicapped patients with multiple sclerosis (MS) were randomly allocated treatment with one or the other drug for a 6-week period. The antispastic effect was evaluated by clinical criteria. The optimal daily dose of both drugs varied considerably from patient to patient, and was on the average 23 mg for Tizanidin and 59 mg for baclofen. To the extent an antispastic effect was observed, the 2 drugs appeared to be equally effective when given at a 1:2 ratio (mg tizanidine: mg baclofen). Side effects of both drugs were sleepiness, muscular weakness and dry mouth. Tizanidine had a mild depressive effect on blood pressure. Sudden withdrawal of both drugs was accompanied by a transient relative increase of spasticity in approximately half the patients. There were no other changes suggesting physical or psychological dependence. The present study underscores that neither baclofen nor tizanidine are ideal antispastic drugs, and emphasize the need for further research.
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PMID:The treatment of spasticity in multiple sclerosis: a double-blind clinical trial of a new anti-spastic drug tizanidine compared with baclofen. 355 79

Tizanidine was evaluated in a prospective, double-blind, randomized, placebo-controlled trial in 187 patients with MS. Taken orally for 9 weeks and preceded by a titration phase for a period of 3 weeks starting at 2 mg daily, tizanidine produced a significant reduction in spastic muscle tone compared with placebo treatment. Within the effective dose range of 24 to 36 mg given daily in three doses, tizanidine achieved a 20% mean reduction in muscle tone. Approximately 75% of patients, with all degrees of spasticity, reported subjective improvement without an increase in muscle weakness, but there was no improvement in activities of daily living depending on movement. Tizanidine achieved its maximum effect on spasticity within 1 week of the start of treatment; the benefit was maintained for at least 1 week after discontinuation of therapy. A variety of adverse events was recorded by patients taking tizanidine, but these were minor and reversible, and rarely limited treatment. Tizanidine is a well-tolerated and effective drug for symptomatic treatment of spasticity.
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PMID:A double-blind, placebo-controlled trial of tizanidine in the treatment of spasticity caused by multiple sclerosis. United Kingdom Tizanidine Trial Group. 797 14

The effects of the intrathecal alpha 2-agonists tizanidine and clonidine and the somatostatin analog octreotide on an experimental rat model of tactile allodynia were investigated to determine the therapeutic potential for treating chronic neuropathic pain. Allodynia was induced by ligating the rat sciatic nerve. The mechanical threshold for paw withdrawal was assessed by applying von Frey hairs to quantify analgesic actions. Mean 50% paw withdrawal thresholds were converted to the percentage of maximum possible effect (%MPE) where %MPE = (postdrug threshold-predrug threshold) divided by (15 g-predrug threshold) x 100. Dose-response curves were plotted for suppression of paw withdrawal 30 minutes after intrathecal injection of various doses of tizanidine, clonidine, and octreotide. Thresholds on the non-lesioned side were greater than 15 g. The lesioned side had baseline thresholds of less than 4.5 g. Dose-response curves were established for the antiallodynia effects of each drug. Tizanidine and clonidine at a 25-micrograms dose increased the threshold to greater than 97% of the MPE, but caused transient hindpaw weakness or sedation. No side effect was observed at a 10-micrograms dose, at which the threshold was 88-96% of MPE. Intrathecal octreotide modestly increased the threshold to only 49-67% of MPE, showing a lesser analgesic effect, although no side effect was observed at a 4-micrograms dose. The antiallodynic effects of intrathecal tizanidine and clonidine were more potent than that of octreotide.
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PMID:Effects of intrathecal nonnarcotic analgesics on chronic tactile allodynia in rats: alpha 2-agonists versus somatostatin analog. 904 98

The central alpha 2 adrenoceptor agonist tizanidine is a myotonolytic agent used in the treatment of spasticity in patients with cerebral or spinal injury. Wide interpatient variability in the effective plasma concentrations of tizanidine means that the optimal dosage must be titrated over 2 to 4 weeks for each patient (dosages of 2 to 36 mg/day have been used in clinical trials). Maximum effects occur within 2 hours of administration. Antispastic efficacy has been demonstrated for tizanidine in placebo-controlled trials, with reduction in mean muscle tone scores of 21 to 37% versus 4 to 9% for patients receiving placebo. Improvement in muscle tone occurred in 60 to 82% of tizanidine recipients, compared with 60 to 65% of baclofen and 60 to 83% of diazepam recipients. Spasm frequency and clonus are also reduced by tizanidine. The most common adverse effects associated with tizanidine are dry mouth and somnolence/drowsiness. Muscle strength, as assessed by objective means, appears not to be adversely affected by tizanidine and subjective muscle weakness is reported less often by tizanidine recipients than by those receiving baclofen or diazepam. Global tolerability was assessed as good to excellent in 44 to 100% of patients receiving tizanidine, compared with 38 to 90% of baclofen and 20 to 54% of diazepam recipients. In conclusion, tizanidine is an antispastic agent with similar efficacy to that of baclofen and a more favourable tolerability profile. While drowsiness is a frequently reported adverse effect with both agents, subjective muscle weakness appears to be less of a problem with tizanidine than with baclofen. Tizanidine, therefore, appears to be an attractive therapeutic alternative for patients with spasticity associated with cerebral or spinal damage.
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PMID:Tizanidine. A review of its pharmacology, clinical efficacy and tolerability in the management of spasticity associated with cerebral and spinal disorders. 907 44

Spasticity and other muscle symptoms in the palliative care patient can contribute to suffering, significantly detracting from overall quality of life. Current therapy primarily includes use of centrally acting muscle relaxants, which are beneficial in treating some symptoms, but frequently have extensive side effects, such as sedation and muscle weakness. Tizanidine, a central alpha 2 adrenergic agonist, has been shown in clinical studies to be as effective as other commonly used antispastic agents, but without debilitating muscle weakness. Tizanidine can cause sedation, which is minimized by dose titration. When taken at night, patients report improvement in getting to sleep and little drowsiness or "hangover sensation" upon waking. Tizanidine is potentially helpful to many palliative care patients with chronic muscle pain and sleep disturbances.
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PMID:Tizanidine in the management of spasticity and musculoskeletal complaints in the palliative care population. 1109 20

The purpose of this research trial is to assess the effectiveness and tolerability of tizanidine in neuropathic pain. In an open-label study, patients with neuropathic pain received 1 to 4 mg of tizanidine once daily for 7 days, followed by weekly dose escalation of 2 to 8 mg to his/her effective or maximum tolerated dose or a maximum of 36 mg over an 8-week period. Treatment effects were assessed, using average weekly pain scores as well as biweekly scores for patient global assessment of pain relief, the neuropathic pain scale, and wisconsin brief pain inventory. Frequency and severity of adverse events were examined also. Twenty-three patients were enrolled. The mean average weekly pain score at baseline was 6.9, which decreased by 1.7 points at the end of week 8 to 5.2 (p < or =.01). A total of 15 patients (68%) reported that their pain relief was improved or much improved with tizanidine therapy, and 2 of these patients became completely pain-free. The following neuropathic pain qualities were significantly lower at week 8 compared with baseline: intense, sharp, hot, dull, cold, sensitive, unpleasant, and deep pain. There was a significant decline in pain quantity and interference of pain on quality of life from baseline to week 8. The mean effective or maximum tolerated dose was 23 mg/day (range 6 to 36 mg/day). Side effects consisted primarily of dizziness/lightheadedness (52%), drowsiness (48%), fatigue/weakness (43%), dry mouth (39%), gastrointestinal upset (30%), and sleep difficulty (22%). One patient developed significant elevation in liver function tests (LFTS) With symptoms at week 4. Tizanidine therapy was discontinued. LFTS returned to normal in 3 weeks. Tizanidine might be an effective treatment for neuropathic pain, offering an alternative for patients poorly responsive to other medications. A larger, randomized placebo-controlled trial is recommended. In addition, comparative studies with alternative agents should be sought.
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PMID:Effectiveness of tizanidine in neuropathic pain: an open-label study. 1462 12

Baclofen is used for treatment of the spasticity of spinal origin that is a common sequela of spinal cord injury and multiple sclerosis; spasticity occurs in about 50% of patients affected by these disorders. In open-label studies of oral baclofen, the drug improved spasticity in 70-87% of patients; additionally, improvement in spasms was reported in 75-96% of patients. In double-blind, crossover, placebo-controlled trials, baclofen was reported to be effective, producing statistically significant improvements in spasticity. Tizanidine is the antispasticity drug that has been most widely compared with oral baclofen; studies have generally found the two drugs to have equivalent efficacy. However, tizanidine has better tolerability, in particular weakness was reported to be occur less frequently with tizanidine than with baclofen. The main adverse effects of oral baclofen include: sedation or somnolence, excessive weakness, vertigo and psychological disturbances. The incidence of adverse effects is reported to range from 10% to 75%. The majority of adverse effects are not severe; most are dose related, transient and/or reversible. The main risks of oral baclofen administration are related to withdrawal: seizures, psychic symptoms and hyperthermia can occur. These symptoms improve after the reintroduction of baclofen, usually without sequelae. When not related to withdrawal; these symptoms mainly present in patients with brain damage and in the elderly. The limited data on baclofen toxicity in patients with renal disease suggest that administration of the drug in these persons may carry an unnecessarily high risk. Intrathecal baclofen is indicated for use in patients with spasticity of spinal origin unresponsive to treatment with maximum doses of oral baclofen, tizanidine and/or dantrolene. The benefits of continuous intrathecal baclofen infusion have been demonstrated: >80% and >65% of patients have improvement in tone and spasms, respectively. The main risks of intrathecal baclofen infusion are symptoms related to overdose or withdrawal; the latter is more important because of the associated severe effects on clinical status and the possibility of death, but it is responsive to rapid treatment. Overdose primarily arises from drug test doses or human error during refill and programming of the pump, and withdrawal most commonly occurs as a result of a problem with the delivery system. Since the adverse consequences do not exceed the benefits of oral and intrathecal baclofen for patients with spinal spasticity, the benefit/risk assessment is favourable.
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PMID:A benefit-risk assessment of baclofen in severe spinal spasticity. 1535 Jan 52